Skip to main content
SpringerLink
Log in

Genetic variants of vitamin D, estrogen α, parathyroid and collagen type I alpha receptor gene and its influence on circulating serum osteocalcin in postmenopausal osteoporosis: A cohort study

  • Original Article
  • Published:
The Nucleus Aims and scope Submit manuscript

Abstract

Osteocalcin is an abundant, highly conserved bone specific protein and the serum levels of OC have been used as a biochemical marker of bone turnover. The genetic variation of certain candidate genes impacts osteocalcin levels in the postmenopausal period and may predispose some women to high bone turnover. To identify the genes influencing variation in serum OC levels, we investigated the polymorphisms of Vitamin D, Estrogen α, Parathyroid and Collagen Type I alpha Receptor genes and its association with bone turnover evaluated by serum osteocalcin in postmenopausal women from south India. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect the polymorphisms at all the four gene receptors (i.e., for VDR, ERα, PTH and COLIA1) in 300 postmenopausal women from South India. Serum osteocalcin levels were measured by immunoassay (ELISA).The serum osteocalcin levels for the Apa I polymorphisms showed varied results, in which, subjects in the control group with “GG” genotype and the osteopenic group with “TT” genotype of the ApaI polymorphism had a significantly higher serum osteocalcin concentration (p < 0.05). The BstBI-AA group in controls had a significantly higher level of serum osteocalcin, this suggests a higher state of bone turnover in the AA genotype. The outcome of this study proposes the probability of a small impact of the VDR- ApaI (GG) genotype, the VDR-TaqI (TT) genotype and the (AA) genotype of the PTH-BstBI polymorphism indicating a higher rate of bone turnover in the healthy postmenopausal women.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

References

  1. Abdi S, Almiman AA, Ansari MGA, Alnaami AM, Mohammed AK, Aljohani NJ, Alenad A, Alghamdi A, Alokail MS, Al-Daghri NM. PTHR1 genetic polymorphisms are associated with osteoporosis among postmenopausal Arab women. BioMed Res Int. 2021. https://doi.org/10.1155/2021/2993761.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Abdi S, Almiman AA, Ansari MGA, Alnaami AM, Mohammed AK, Aljohani NJ, Alenad A, Alghamdi A, Alokail MS, Al-Daghri NM. PTHR1 genetic polymorphisms are associated with osteoporosis among postmenopausal arab women. Biomed Res Int. 2021;2021:2993761. https://doi.org/10.1155/2021/2993761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Almeida M, Iyer S, Martin-Millan M, Bartell SM, Han L, Ambrogini E, Onal M, Xiong J, Weinstein RS, Jilka RL, O’Brien CA, Manolagas SC. Estrogen receptor-α signaling in osteoblast progenitors stimulates cortical bone accrual. J Clin Investig. 2013;123(1):394–404. https://doi.org/10.1172/JCI65910.

    Article  CAS  PubMed  Google Scholar 

  4. Aloubaidy R. Osteocalcin level and its association with vitamin D receptor gene polymorphisms (TaqI and ApaI) in Iraqi obese type 2 diabetes mellitus. Int J Sci Res (IJSR). 2017;6:1599–604.

    Article  Google Scholar 

  5. Eastell R, Hannon RA. Biomarkers of bone health and osteoporosis risk. Proc Nutr Soc. 2008;67(2):157–62.

    Article  PubMed  Google Scholar 

  6. Fernandez C, Tennyson J, Priscilla AS. Osteoporosis and its association with vitamin D receptor, oestrogen α receptor, parathyroid receptor and collagen type I alpha receptor gene polymorphisms with bone mineral density: a pilot study from south Indian postmenopausal women of Tamil Nadu. Biochem Genet. 2022. https://doi.org/10.1007/s10528-022-10197-5.

    Article  PubMed  Google Scholar 

  7. Garnero P, Borel O, Grant SF, Ralston SH, Delmas PD. Collagen Ia1 Sp1 polymorphism, bone mass, and bone turnover in healthy French premeno pausal women: the OFELY study. J Bone Miner Res. 1998;13(813–817):37.

    Google Scholar 

  8. Garnero P, Borel O, Sornay-Rendu E, Arlot ME, Delmas PD. Vitamin D receptor gene polymorphisms are not related to bone turnover, rate of bone loss, and bone mass in postmenopausal women: the OFELY Study. J Bone Miner Res. 1996;11:827–34.

    Article  CAS  PubMed  Google Scholar 

  9. Griesmacher A, Peichl P, Pointinger P. Biochemical markers in menopausal women. Scand J Clin Lab Investig. 1997;227:64–72.

    Article  CAS  Google Scholar 

  10. Han KO, Moon IG, Kang YS, Chung HY, Min HK, Han IK. Nonassociation of estrogen receptor genotypes with bone mineral density and estrogen responsiveness to hormone replacement therapy in Korean postmenopausal women. J Clin Endocrinol Metab. 1997;82:991–5.

    Article  CAS  PubMed  Google Scholar 

  11. Hong EP, Park JW. Sample size and statistical power calculation in genetic association studies. Genom Inform. 2012;10(2):117–22.

    Article  Google Scholar 

  12. Ioannidis JP, Ng MY, Sham PC, Zintzaras E, Lewis CM, Deng HW, Econs MJ, Karasik D, Devoto M, Kammerer CM, Spector T, Andrew T, Cupples LA, Duncan EL, Foroud T, Kiel DP, Koller D, Langdahl B, Mitchell BD, Peacock M, Ralston SH. Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass. J Bone Miner Res Off J Am Soc Bone Miner Res. 2007;22(2):173–83.

    Article  CAS  Google Scholar 

  13. Kalaiselvi VS, Prabhu K, Ramesh M, Venkatesan V. The association of serum osteocalcin with the bone mineral density in postmenopausal women. J Clin Diagn Res JCDR. 2013;7(5):814–6. https://doi.org/10.7860/JCDR/2013/5370.2946.

    Article  CAS  Google Scholar 

  14. Kamel HK. Postmenopausal osteoporosis: etiology, current diagnostic strategies, and nonprescription interventions. J Manag Care Pharmacy JMCP. 2006;12(6 Suppl A):S4–28.

    Article  Google Scholar 

  15. Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res Off J Am Soc Bone Miner Res. 1994;9(8):1137–41.

    Article  CAS  Google Scholar 

  16. Kelly PJ, Hopper JL, Macaskill GT, Pocock NA, Sambrook PN, Eisman JA. Genetic factors in bone turnover. J Clin Endocrinol Metab. 1991;72:808–13.

    Article  CAS  PubMed  Google Scholar 

  17. Kobayashi S, Inoue S, Hosoi T, Ouchi Y, Shiraki M, Orimo H. Association of bone mineral density with polymorphism of the estrogen receptor gene. J Bone Miner Res. 1996;11(306–311):38.

    Google Scholar 

  18. Li WF, Hou SX, Yu B, Li MM, Férec C, Chen JM. Genetics of osteoporosis: accelerating pace in gene identification and validation. Hum Genet. 2010;127(3):249–85.

    Article  CAS  PubMed  Google Scholar 

  19. Lian JB, Friedman PA. The vitamin K-dependent synthesis of gamma-carboxyglutamic acid by bone microsomes. J Biol Chem. 1978;253(19):6623–6. https://doi.org/10.1016/S0021-9258(17)37956-5.

    Article  CAS  PubMed  Google Scholar 

  20. Liao J, Qin Q, Zhou Y, et al. Vitamin D receptor Bsm I polymorphism and osteoporosis risk in postmenopausal women: a meta-analysis from 42 studies. Genes Nutr. 2020;15:20. https://doi.org/10.1186/s12263-020-00679-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Liu L, Webster TJ. In situ sensor advancements for osteoporosis prevention, diagnosis, and treatment. Curr Osteoporos Rep. 2016;14(6):386–95.

    Article  PubMed  Google Scholar 

  22. Mitchell BD, Cole SA, Bauer RL, Iturria SJ, Rodriguez EA, Blangero J, MacCluer JW, Hixson JE. Genes influencing variation in serum osteocalcin concentrations are linked to markers on chromosomes 16q and 20q. J Clin Endocrinol Metab. 2000;85(4):1362–6. https://doi.org/10.1210/jcem.85.4.6571.

    Article  CAS  PubMed  Google Scholar 

  23. Morrison NA, Yeoman R, Kelly PJ, Eisman JA. Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci USA. 1992;89(15):6665–9. https://doi.org/10.1073/pnas.89.15.6665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nishimoto SK, Price PA. Secretion of the vitamin K-dependent protein of bone by rat osteosarcoma cells. Evidence for an intracellular precursor. J Biol Chem. 1980;255(14):6579–83. https://doi.org/10.1016/S0021-9258(18)43608-3.

    Article  CAS  PubMed  Google Scholar 

  25. Ralston SH, Uitterlinden AG. Genetics of osteoporosis. Endocr Rev. 2010;31(5):629-662.4.

    Article  CAS  PubMed  Google Scholar 

  26. Rapuri PB, Gallagher JC, Knezetic JA, Haynatzka V. Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen. Maturitas. 2006;53(4):371–9. https://doi.org/10.1016/j.maturitas.2005.07.007.

    Article  CAS  PubMed  Google Scholar 

  27. Rivera-Leon EA, Palmeros-Sanchez B, Llamas-Covarrubias IM, Fernandez S, Armendariz-Borunda J, Gonzalez-Hita M, Bastidas-Ramirez BE, Zepeda-Moreno A, Sanchez-Enriquez S. Vitamin-D receptor gene polymorphisms (TaqI and ApaI) and circulating osteocalcin in type 2 diabetic patients and healthy subjects. Endokrynol Pol. 2015;66(4):329–33. https://doi.org/10.5603/EP.2015.0042.

    Article  PubMed  Google Scholar 

  28. Saoji R, Desai M, Das RS, Das TK, Khatkhatay MI. Estrogen receptor α and β gene polymorphism in relation to bone mineral density and lipid profile in Northeast Indian women. Gene. 2019;710:202–9. https://doi.org/10.1016/j.gene.2019.05.060.

    Article  CAS  PubMed  Google Scholar 

  29. Sapir-Koren R, Livshits G, Kobyliansky E. Genetic effects of estrogen receptor alpha and collagen IA1 genes on the relationships of parathyroid hormone and 25 hydroxyvitamin D with bone mineral density in Caucasian women. Metab Clin Exp. 2003;52(9):1129–35.

    Article  CAS  PubMed  Google Scholar 

  30. Sheehan D, Bennett T, Cashman K. The genetics of osteoporosis: vitamin D receptor gene polymorphisms and circulating osteocalcin in healthy Irish adults. Ir J Med Sci. 2001;170:54–7. https://doi.org/10.1007/BF0316772321.

    Article  CAS  PubMed  Google Scholar 

  31. Sowers M, Jannausch ML, Liang W, Willing M. Estrogen receptorgenotypes and their association with the 10 year changesin bone mineral density and osteocalcin concentrations. J ClinEndocrinolMetab. 2004;89(2):733.

    Article  CAS  Google Scholar 

  32. Stewart TL, Ralston SH. Role of genetic factors in the pathogenesis of osteoporosis. J Endocrinol. 2000;166(2):235–45. https://doi.org/10.1677/joe.0.1660235.

    Article  CAS  PubMed  Google Scholar 

  33. Suguna S, Kamble S, Bharatha A. Genomic DNA isolation from human whole blood samples by non-enzymatic salting out method. Int J Pharm Pharm Sci. 2014;6(6):198–9.

    Google Scholar 

  34. Trajkovic K, Perovic M, Tarasjev A, Pilipovic N, Popovic V, Kanazir S. Association of collagen type I alpha1 gene polymorphism with bone mineral density in osteoporotic women in Serbia. J Women’s Health. 2010;19(7):1299–303. https://doi.org/10.1089/jwh.2009.1698.

    Article  Google Scholar 

  35. Willing M, Sowers M, Aron D, Clark MK, Burns T, Bunten C, Crutchfield M, D’Agostino D, Jannausch M. Bone mineral density and its change in white women: estrogen and vitamin D receptor genotypes and their interaction. J Bone Miner Res. 1998;13:695–705. https://doi.org/10.1359/jbmr.1998.13.4.695.

    Article  CAS  PubMed  Google Scholar 

  36. Wilson SG, Reed PW, Andrew T, Barber MJ, Lindersson M, Langdown M, Thompson D, Thompson E, Bailey M, Chiano M, Kleyn PW. A genome-screen of a large twin cohort reveals linkage for quantitative ultrasound of the calcaneus to 2q33–37 and 4q12–21. J Bone Miner Res. 2004;19:270–7.

    Article  CAS  PubMed  Google Scholar 

  37. Zheng HF, Spector TD, Richards JB. Insights into the genetics of osteoporosis from recent genome-wide association studies. Expert Rev Mol Med. 2011;13: e28.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors express their sincere thanks to Indian Council of Medical Research for funding this work. The authors also sincerely thank the Principal, Lady Doak College and the management for providing the research facilities to carry out this work. The authors would like to place on record their deepest gratitude to Dr. S. Pugalanthi Pandian, Managing Director, Pandian Advanced Medical Centre for being the clinical advisor for this study.

Funding

This work was supported by Indian Council of Medical Research (ICMR) (NO3/1/2/6/SRF/ORTHO/2018-NCD-I).

Author information

Authors and Affiliations

  1. Department of Zoology and Research Centre, Lady Doak College, Madurai, Tamil Nadu, 625002, India

    Chrisanne Freeman & A. S. Priscilla

  2. Department of Plant Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625021, India

    Chrisanne Freeman & Jebasingh Tennyson

  3. Department of Biotechnology, Bishop Heber College, Tiruchirappalli, Tamil Nadu, 620017, India

    Chrisanne Freeman

Authors
  1. Chrisanne Freeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jebasingh Tennyson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. S. Priscilla
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CF devised and performed the experiments and data analysis; JT designed and PAS supervised and managed all studies. All the authors contributed towards writing the manuscript.

Corresponding author

Correspondence to A. S. Priscilla.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

Authors declare that they have no conflict of interest.

Additional information

Corresponding Editor: Somnath Paul; Reviewers: Neerja Katiyar, Ishita Rehman, Neha Kachewar.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Freeman, C., Tennyson, J. & Priscilla, A.S. Genetic variants of vitamin D, estrogen α, parathyroid and collagen type I alpha receptor gene and its influence on circulating serum osteocalcin in postmenopausal osteoporosis: A cohort study. Nucleus (2024). https://doi.org/10.1007/s13237-023-00456-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13237-023-00456-0

Keywords

Search

Navigation